犬Mast细胞癌表观遗传标记的预后价值。
Prognostic value of epigenetic markers for canine mast cell cancer.
发表日期:2023
作者:
Shahzar Syed, Britta J Knight, Geoffrey A Wood, Brenda Lynn Coomber
来源:
Epigenetics & Chromatin
摘要:
犬体肥大细胞瘤(MCTs)约占所有犬皮肤肿瘤的21%。尽管存在全面的分级系统,但有时很难预测生物学侵袭性,因此需要更好的预后标志物。各种癌症的进展涉及DNA高甲基化,低甲基化和表观遗传酶失调。因此,全球水平的5-甲基胞嘧啶,5-羟甲基胞嘧啶和相关的酶DNMT1以及IDH1表达可能预测MCT的侵袭性。一个由244个不同肿瘤样本的核心组成的组织微阵列(TMA)来自189只狗,它们被免疫标记并用于量化全球DNA甲基化和羟甲基化水平以及DNA甲基化涉及的酶的水平及其与犬MCT结果的关系。从免疫标记的TMA中,使用QuPath(v0.1.2)生成H分数,并与相关患者数据一起分析。在所有犬MCT病例中,高5MC和DNMT1以及低IDH1水平与较差的预后相关。高5MC水平显示皮下病例疾病无瘤期短的重要性,高5MC水平显示在Kiupel分级系统高级别病例中DFI和总生存率较差。在Patnaik分级系统中,II级病例DNMT1水平低的DFI更好,5MC和5HMC水平低的OS更好。对于接受手术外辅助疗法的病例,除IDH1外的所有参数都与OS显着相关。因此,DNA甲基化状态和与DNA甲基化途径相关的酶的水平有潜力更好地预测犬MCT的预后,并可能影响治疗决策。版权所有:©2023 Syed等。这是根据知识共享署名许可的开放获取文章,允许在任何媒介上自由使用,分发和复制,前提是原始作者和来源得到良好的归属。
Canine Mast cell tumors (MCTs) constitute approximately 21% of all canine skin tumors. Despite the use of comprehensive grading systems, biological aggressiveness is sometimes difficult to predict, therefore there is a need for better prognostic markers. Progression in various cancers involves DNA hypermethylation, hypomethylation and epigenetic enzyme dysregulation. Therefore, global levels of 5-methylcytosine, 5-hydroxymethylcytosine and associated enzymes DNMT1, and IDH1 expression may predict MCT aggressiveness. A tissue microarray (TMA) with cores from 244 different tumor samples from 189 dogs was immunolabelled and used to quantify the global DNA methylation and hydroxymethylation levels as well as the levels of the enzymes involved in DNA methylation and their relationship with canine MCT outcome. From the immunolabelled TMA, H-scores were generated using QuPath (v0.1.2) and analyzed with associated patient data. High 5MC and DNMT1, and low IDH1 levels were associated with poorer outcome when looking at all canine MCT cases. High 5MC levels showed significance for shorter disease-free interval (DFI) in subcutaneous cases and high 5MC levels showed poorer DFI and overall survival (OS) in cases with Kiupel's grading system high grade. Cases with grade II in Patnaik's grading system showed better DFI with low levels of DNMT1 and better OS with low levels of 5MC and 5HMC. High levels of DNMT1 staining were also associated with shorter DFI for dermal MCTs. For cases that received adjuvant therapy in addition to surgery, all parameters except IDH1 were significantly associated with OS. Therefore, there is potential for DNA methylation status and levels of enzymes associated with DNA methylation pathways to better predict outcome in canine MCT, and to possibly influence treatment decisions.Copyright: © 2023 Syed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.